Clinical Question: Does cardiac resynchronization improve outcomes in patients with moderately severe to severe heart failure?

Setting: Inpatient (any location) with outpatient follow-up

Study Design: Randomized controlled trial (nonblinded)

Synopsis: Cardiac resynchronization is thought to improve outcomes in patients with heart failure and interventricular conduction delay by improving left ventricular systolic function. The authors studied a select subset of patients with heart failure who had a New York Heart Association functional classification of III or IV, an ejection fraction of less than 35 percent, a QRS interval of at least 120 milliseconds, a PR interval of at least 150 milliseconds, sinus rhythm, hospitalization for heart failure within the past year, and no other indication for a pacemaker or implantable defibrillator. Patients were randomized to receive optimal medical management (n = 308), optimal medical management plus pacemaker (n = 617), or optimal medical management plus pacemaker/defibrillator (n = 595). Allocation concealment was not described, and outcomes were adjudicated by researchers not blinded to treatment assignment. (While not an issue for the most important outcome—all-cause mortality—it might be an issue for the combined outcome of mortality plus rehospitalization.) The mean age of the participants was 67 years, two thirds were men, and groups were balanced at the start of the study; analysis was by intention to treat.

Patients in the medication-only group were much more likely to withdraw from the study than the patients in the other two groups (26 percent versus 6 percent and 7 percent), probably because the devices became commercially available during the study period, and the study was not blinded. Patients were followed up for an average of 11.9 months in the medication group, 16.2 months in the pacemaker group, and 15.7 months in the pacemaker/defibrillator group. Primary outcomes were assessed at 12 months of follow-up.

All-cause mortality was lower in the two pacemaker groups: 19 percent for medication only, 15 percent for pacemaker (P = .059; absolute risk reduction [ARR] = 4 percent; number needed to treat [NNT] = 25), and 12 percent for pacemaker/defibrillator (P = .003; ARR = 7 percent; NNT= 14). The combined end points of death from any cause or hospitalization for any reason also were more common in the medication-only group than in either of the pacemaker groups (68 percent versus 56 percent; ARR = 12 percent; NNT = eight). Adverse events were more common in the pacemaker groups: 61 percent for medication only, 66 percent for pacemaker, and 69 percent for pacemaker/defibrillator. The comparison between medication and pacemaker/defibrillator was statistically significant.

Bottom Line: Cardiac resynchronization reduces mortality and the likelihood of hospitalization in patients with heart failure and interventricular conduction delay. Use of a combined pacemaker/defibrillator was the most effective treatment (NNT = 14 for one year). (Level of Evidence: 1b–)